PMID- 23737213
OWN - NLM
STAT- MEDLINE
DCOM- 20131101
LR  - 20220321
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 52
IP  - 8
DP  - 2013 Aug
TI  - Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid 
      hemangioendothelioma.
PG  - 775-84
LID - 10.1002/gcc.22073 [doi]
AB  - Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive 
      morphologic appearance and are characterized by a recurrent t(1;3) translocation, 
      resulting in a WWTR1-CAMTA1 fusion gene. We have recently encountered a 
      fusion-negative subset characterized by a somewhat different morphology, 
      including focally well-formed vasoformative features, which was further 
      investigated for recurrent genetic abnormalities. Based on a case showing strong 
      transcription factor E3 (TFE3) immunoreactivity, fluorescence in situ 
      hybridization (FISH) analysis for TFE3 gene rearrangement was applied to the 
      index case as well as to nine additional cases, selected through negative 
      WWTR1-CAMTA1 screening. A control group, including 18 epithelioid hemangiomas, 
      nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. 
      TFE3 gene rearrangement was identified in 10 patients, with equal gender 
      distribution and a mean age of 30 years old. The lesions were located in somatic 
      soft tissue in six cases, lung in three and one in bone. One case with available 
      frozen tissue was tested by RNA sequencing and FusionSeq data analysis to detect 
      novel fusions. A YAP1-TFE3 fusion was thus detected, which was further validated 
      by FISH and reverse transcription polymerase chain reaction (RT-PCR). YAP1 gene 
      rearrangements were then confirmed in seven of the remaining nine TFE3-rearranged 
      EHEs by FISH. No TFE3 structural abnormalities were detected in any of the 
      controls. The TFE3-rearranged EHEs showed similar morphologic features with at 
      least focally, well-formed vascular channels, in addition to a variably solid 
      architecture. All tumors expressed endothelial markers, as well as strong nuclear 
      TFE3. In summary, we are reporting a novel subset of EHE occurring in young 
      adults, showing a distinct phenotype and YAP1-TFE3 fusions.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Antonescu, Cristina R
AU  - Antonescu CR
AD  - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 
      10021, USA. antonesc@mskcc.org
FAU - Le Loarer, Francois
AU  - Le Loarer F
FAU - Mosquera, Juan-Miguel
AU  - Mosquera JM
FAU - Sboner, Andrea
AU  - Sboner A
FAU - Zhang, Lei
AU  - Zhang L
FAU - Chen, Chun-Liang
AU  - Chen CL
FAU - Chen, Hsiao-Wei
AU  - Chen HW
FAU - Pathan, Nursat
AU  - Pathan N
FAU - Krausz, Thomas
AU  - Krausz T
FAU - Dickson, Brendan C
AU  - Dickson BC
FAU - Weinreb, Ilan
AU  - Weinreb I
FAU - Rubin, Mark A
AU  - Rubin MA
FAU - Hameed, Meera
AU  - Hameed M
FAU - Fletcher, Christopher D M
AU  - Fletcher CD
LA  - eng
GR  - R01 CA152057/CA/NCI NIH HHS/United States
GR  - P01CA47179/CA/NCI NIH HHS/United States
GR  - P50 CA 140146-01/CA/NCI NIH HHS/United States
GR  - P01 CA047179/CA/NCI NIH HHS/United States
GR  - P50 CA140146/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130605
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Phosphoproteins)
RN  - 0 (TFE3 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Adolescent
MH  - Adult
MH  - Base Sequence
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics
MH  - Female
MH  - Gene Rearrangement/genetics
MH  - Hemangioendothelioma, Epithelioid/diagnosis/*genetics/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kidney Neoplasms/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/*genetics/isolation & purification
MH  - Phosphoproteins/*genetics
MH  - Sequence Analysis, RNA
MH  - Transcription Factors
MH  - Translocation, Genetic/genetics
MH  - YAP-Signaling Proteins
PMC - PMC4089994
MID - NIHMS585490
COIS- Conflict of interest: none
EDAT- 2013/06/06 06:00
MHDA- 2013/11/02 06:00
PMCR- 2014/07/09
CRDT- 2013/06/06 06:00
PHST- 2013/04/15 00:00 [received]
PHST- 2013/04/22 00:00 [accepted]
PHST- 2013/06/06 06:00 [entrez]
PHST- 2013/06/06 06:00 [pubmed]
PHST- 2013/11/02 06:00 [medline]
PHST- 2014/07/09 00:00 [pmc-release]
AID - 10.1002/gcc.22073 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2013 Aug;52(8):775-84. doi: 10.1002/gcc.22073. Epub 
      2013 Jun 5.